Analysis of the C. elegans Argonaute Family Reveals that Distinct Argonautes Act Sequentially during RNAi

Yigit, E., Batista, P. J., Bei, Y., Pang, K. M., Chen, C. C. G., Tolia, N. H., Joshua-Tor, L., Mitani, S., Simard, M. J., Mello, C. C. (2006) Analysis of the C. elegans Argonaute Family Reveals that Distinct Argonautes Act Sequentially during RNAi. Cell, 127 (4). pp. 747-757. ISSN 00928674

Abstract

Argonaute (AGO) proteins interact with small RNAs to mediate gene silencing. C. elegans contains 27 AGO genes, raising the question of what roles these genes play in RNAi and related gene-silencing pathways. Here we describe 31 deletion alleles representing all of the previously uncharacterized AGO genes. Analysis of single- and multiple-AGO mutant strains reveals functions in several pathways, including (1) chromosome segregation, (2) fertility, and (3) at least two separate steps in the RNAi pathway. We show that RDE-1 interacts with trigger-derived sense and antisense RNAs to initiate RNAi, while several other AGO proteins interact with amplified siRNAs to mediate downstream silencing. Overexpression of downstream AGOs enhances silencing, suggesting that these proteins are limiting for RNAi. Interestingly, these AGO proteins lack key residues required for mRNA cleavage. Our findings support a two-step model for RNAi, in which functionally and structurally distinct AGOs act sequentially to direct gene silencing. © 2006 Elsevier Inc. All rights reserved.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > AGO
organism description > animal > C elegans
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > sRNA
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 05 Dec 2011 21:50
Last Modified: 13 Jan 2017 21:10
Related URLs:
URI: https://repository.cshl.edu/id/eprint/22941

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